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Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis (VALIANT)

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ClinicalTrials.gov Identifier: NCT05067127
Recruitment Status : Active, not recruiting
First Posted : October 5, 2021
Last Update Posted : March 12, 2024
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Study Description
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Brief Summary:
This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.

Condition or disease Intervention/treatment Phase
C3G IC-MPGN C3 Glomerulopathy C3 Glomerulonephritis Complement 3 Glomerulopathy Complement 3 Glomerulopathy (C3G) Complement 3 Glomerulonephritis Dense Deposit Disease DDD Membranoproliferative Glomerulonephritis Membranoproliferative Glomerulonephritis (MPGN) Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) Drug: Pegcetacoplan Other: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
Actual Study Start Date : November 12, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Group 1: Pegcetacoplan administration
Subcutaneous infusion of 20mL (1080 mg), twice weekly (for adults or adolescents >50kg), and the three other weight-based doses either of 10mL (540mg), 12mL (648mg), or 15mL (810mg)
 Drug: Pegcetacoplan
Complement (C3) Inhibitor
Placebo Comparator: Group 2: Placebo administration
Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly
 Other: Placebo
Sterile solution of equal volume to active arm


Outcome Measures
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Primary Outcome Measures :
  1. The log-transformed ratio of uPCR at week 26 compared to baseline [ Time Frame: Baseline to week 26 ]

Secondary Outcome Measures :
  1. The proportion of participants who meet the criteria for achieving a composite renal endpoint (a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and a ≥50% reduction in uPCR compared to the baseline visit.) [ Time Frame: Baseline to week 26 ]
  2. The proportion of participants with a reduction of at least 50% from baseline in uPCRF [ Time Frame: Baseline to week 26 ]
  3. Change from baseline in eGFR [ Time Frame: Baseline to week 26 ]
  4. For participants with evaluable renal biopsies, the change from baseline in the activity score of the C3G histologic index score [ Time Frame: Baseline to week 26 ]
  5. The proportion of participants with evaluable renal biopsies showing decreases in C3c staining on renal biopsy from baseline [ Time Frame: Baseline to week 26 ]

Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
  2. A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).

  3. Evidence of active renal disease, based on one or more of the following:

    1. In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2+ C3c staining on the baseline renal biopsy.

    2. In adolescents not providing a baseline renal biopsy, at least one of the following:

      • Plasma sC5b-9 level above the upper limit of normal during screening
      • Serum C3 below the LLN during screening
      • Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysis of urine.
      • Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history.
  4. No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
  5. At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.
  6. eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.

  7. Stable regimen for C3G/IC-MPGN treatment, as described below:

    1. Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization
    2. Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 812 weeks prior to the baseline renal biopsy and randomization.
    3. If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.
  8. Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.

Exclusion Criteria:

  1. Previous exposure to pegcetacoplan.
  2. C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.
  3. Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.
  4. Body weight greater than 100 kg at screening.
  5. Hypersensitivity to pegcetacoplan or to any of the excipients.
  6. History of meningococcal disease.

  7. Malignancy, except for the following:

    1. Cured basal or squamous cell skin cancer
    2. Curatively treated in situ disease
    3. Malignancy-free and off treatment for ≥5 years
  8. Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
  9. An absolute neutrophil count <1000 cells/mm3 at screening.
  10. Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.
  11. Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug.
  12. Presence or suspicion of severe infection during the screening period (including but not limited to recurrent or chronic infections) that, in the opinion of the investigator, may place the participant at unacceptable risk by study participation.
  13. Known or suspected hereditary fructose intolerance.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05067127


Locations
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Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
More Information
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Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05067127    
Other Study ID Numbers: APL2-C3G-310
First Posted: October 5, 2021    Key Record Dates
Last Update Posted: March 12, 2024
Last Verified: March 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
 Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Immune System Diseases